Fig. 3. Overexpression of HDAC4 and 5 in skeletal muscle inhibits oxidative glucose utilisation.

A Experimental overview of vehicle/insulin and isotopic glucose tracer administration in the bilateral AAV6 HDAC4 and 5 overexpression model. B 2-deoxyglucose (2-DG) clearance in tibialis anterior (TA) skeletal muscle of bilateral AAV6 HDAC4 and 5 mice administered vehicle or insulin and isotopic glucose tracers (Two-way ANOVA, genotype F(1,27) = 5.061). C 2-DG clearance in TA skeletal muscle overexpressing HDAC4 and 5 relative to Control (Paired t-test). D ¹⁴C-glucose incorporation into glycogen in TA skeletal muscle of bilateral AAV6 HDAC4 and 5 mice administered vehicle or insulin and isotopic glucose tracers (Two-way ANOVA, genotype F(1,24) = 4.864). E ¹⁴C-glucose incorporation into lipid in TA skeletal muscle of bilateral AAV6 HDAC4 and 5 mice administered vehicle or insulin and isotopic glucose tracers (Two-way ANOVA, insulin F(1,21) = 14.94). F Representative images of insulin signalling components in TA skeletal muscle of bilateral AAV6 HDAC4 and 5 mice administered vehicle or insulin and isotopic glucose tracers and quantification of (G) pT308 Akt (Two-way ANOVA, insulin F(1,27) = 13.75); (H) pS473 Akt (Two-way ANOVA, insulin F(1,28) = 33.13), and; (I) pS642 TBC1D4 (Two-way ANOVA, genotype F(1,25) = 13.60). J Experimental overview of stable isotope metabolomics in the bilateral AAV6 HDAC4 and 5 overexpression model administered U¹³C-glucose. K Total metabolite abundance in TA skeletal muscle of bilateral AAV6 HDAC4 and 5 mice administered U¹³C-glucose. (Paired t-tests). L Total ¹³C labelling of glycolytic and TCA cycle metabolites in TA skeletal muscle of bilateral AAV6 HDAC4 and 5 mice administered U¹³C-glucose. (Paired t-tests). Isotopologues of (M) Lactate; (N) Succinate, and; (O) Malate (Paired t-tests) in TA skeletal muscle of bilateral AAV6 HDAC4 and five mice administered U¹³C-glucose. Data are mean ± SEM, n = 5–8 per group.